Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental evaluation demonstrated that suspended growth systems operated in a two-tank accelerator/aerator configuration significantly increased the overall removal rates for phenol and 2,4-dichlorophenol (2,4-DCP), aromatic hydrocarbons that require initial monooxygenations. The accelerator tank is a small volume that receives the influent and recycled biomass. It has a high ratio of electron donor (BOD) to electron acceptor (O2). Biomass in the accelerator should be enriched in reduced nicotinamide adenine dinucleotide (NADH + H+) and have a very high specific growth rate, conditions that should accelerate the kinetics of monooxygenation reactions. For the more slowly degraded 2,4-DCP, the average percentage removal increased from 74% to 93%, even though the volume of the two-tank system was smaller than that of the one-tank system in most experiments. The average volumetric and biomass-specific removal rates increased by 50% and 100%, respectively, in the two-tank system, compared to a one-tank system. The greatest enhancement in 2,4-DCP removal occurred when the accelerator tank comprised approximately 20% of the system volume. Biomass in the accelerator tank was significantly enriched in NADH + H+ when its dissolved oxygen (DO) concentration was below 0.25 mg/L, a situation having a high ratio of donor to acceptor. The accelerator biomass had its highest NADH + H+ content for the experiments that had the highest rate of 2,4-DCP removal. Biomass in the accelerator also had a much higher specific growth rate than in the aerator or the system overall, and the specific growth rate in the accelerator was inversely correlated to the accelerator volume.
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PMID:Two-tank suspended growth process for accelerating the detoxification kinetics of hydrocarbons requiring initial monooxygenation reactions. 1244 13

The mechanisms underlying the observed acceleration of monooxygenation reactions in two-tank accelerator/aerator suspended growth system are evaluated in detail. The accelerator tank is characterized by a very high electron flow through reduced nicotinamide adenine dinucleotide (NADH + H+), particularly when the retention-time ratio is small. Only a small fraction of the electron flow was diverted to oxygenation reactions, and the major sinks of NADH + H+ were respiration and biomass synthesis. The main producer of NADH + H+ is oxidation of acetate, a rapidly degraded electron-donor substrate. The half-maximum-rate concentration for oxygen used in respiration was 0.03 mg/L, while the half-maximum-rate concentration for oxygen used as a cosubstrate in monooxygenation was 0.18 mg/L. Thus, monooxygenations were more sensitive to oxygen limitation than was respiration. The NADH + H+ concentration had a direct effect on the monooxygenation kinetics. The rate coefficients for both monooxygenation reactions were directly proportional to the specific growth rate in the accelerator, which supports that the accelerator tank caused an up-regulation of the monooxygenase content. Because the rate coefficients in the aerator tank were much larger than in the one-tank system, even though the specific growth rates were nearly the same, monooxygenases may have carried over from the accelerator tank to the aerator tank. Its higher concentration of 2,4-dichlorophenol (2,4-DCP) and the higher specific growth rate were the main reasons why the accelerator had faster kinetics for 2,4-DCP utilization than did the aerator tank. The apparently higher levels of monooxygenase in both tanks of the two-tank system also appears be a primary reason why its performance was substantially superior to that of the one-tank system in terms of 2,4-DCP removal.
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PMID:A detailed analysis of the mechanisms controlling the acceleration of 2,4-DCP monooxygenation in the two-tank suspended growth process. 1244 14

This study investigated the effect of reduced free fatty acid (FFA) availability on pyruvate dehydrogenase activation (PDHa) and carbohydrate metabolism during moderate aerobic exercise. Eight active male subjects cycled for 40 min at 55% Vo(2 peak) on two occasions. During one trial, subjects ingested 20 mg/kg body mass of the antilipolytic drug nicotinic acid (NA) during the hour before exercise to reduce FFA. Nothing was ingested in the control trial (CON). Blood and expired gas measurements were obtained throughout the trials, and muscle biopsy samples were obtained immediately before exercise and at 5, 20, and 40 min of exercise. Plasma FFA were lower in the NA trial (0.13 +/- 0.01 vs. 0.48 +/- 0.03 mM, P < 0.05), and the respiratory exchange ratio (RER) was increased with NA (0.93 +/- 0.01 vs. 0.89 +/- 0.01, P < 0.05), resulting in a 14.5 +/- 1.8% increase in carbohydrate oxidation compared with CON. PDHa increased rapidly in both trials at exercise onset but was approximately 15% higher (P < 0.05) throughout exercise in the NA trial (2.44 +/- 0.19 and 2.07 +/- 0.12 mmol x kg wet muscle(-1) x min(-1) for NA and CON at 40 min). Muscle glycogenolysis was 15.3 +/- 9.6% greater in the NA trial vs. the CON trial but did not reach statistical significance. Glucose 6-phosphate contents were elevated (P < 0.05) in the NA trial at 30 and 40 min of exercise, but pyruvate and lactate contents were unaffected. These data demonstrate that the reduction of exogenous FFA availability increased the activation of PDH and carbohydrate oxidation during moderate aerobic exercise in men. The increased activation of PDH was not explained by changes in muscle pyruvate or the ATP/ADP ratio but may be related to a decrease in the NADH/NAD(+) ratio or an epinephrine-induced increase in calcium concentration.
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PMID:Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise. Pyruvate dehydrogenase. 1255 53

The production of NO by heart mitochondria was 0.7-1.1 nmol NO/min.mg protein, an activity similar to the ones observed in mitochondrial membranes from other organs. Heart mtNOS seems to contribute with about 56% of the total cellular NO production. The immunological nature of the mtNOS isoform of cardiac tissue remains unclear; in our laboratory, heart mtNOS reacted with an anti-iNOS anti-body. Heart mtNOS expression and activity are regulated by physiological and pharmacological effectors. The state 4/state 3 transition regulates heart mtNOS activity and NO release in intact respiring mitochondria: NO production rates in state 3 were 40% lower than in state 4. Heart mtNOS expression was selectively regulated by O(2) availability in hypobaric conditions and the activity was 20-60% higher in hypoxic rats than in control animals, depending on age. In contrast, NADH-cytochrome c reductase and cytochrome oxidase activities were not affected by hypoxia. The activity of rat heart mtNOS decreased 20% on aging from 12 to 72 weeks of age. On the pharmacological side, mitochondrial NO production was increased after enalapril treatment (the inhibitor of the angiotensin converting enzyme) with modification of heart mtNOS functional activity in the regulation of mitochondrial O(2) uptake and H(2)O(2) production. Thus, heart mtNOS is a highly regulated mitochondrial enzyme, which in turn, plays a regulatory role through mitochondrial NO steady state levels that modulate O(2) uptake and O(2)(-) and H(2)O(2) production rates. Nitric oxide and H(2)O(2) constitute signals for metabolic control that are involved in the regulation of cellular processes, such as proliferation and apoptosis.
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PMID:Heart mitochondrial nitric oxide synthase. Effects of hypoxia and aging. 1505 16

R-2-hydroxy-4-phenylbutyric acid (R-HPBA) is an important intermediate in the manufacture of angiotensin converting enzyme inhibitors. In this work, a recombinant D-lactate dehydrogenase (LDH) was used to transform 2-oxo-4-phenylbutyric acid (OPBA) to R-HPBA, with concomitant oxidation of beta-nicotinamide adenine dinucleotide (NADH) to NAD(+). The cofactor NADH was regenerated by formate dehydrogenase (FDH) present in whole cells of Candida boidinii, which were pre-treated with toluene to make them permeable. The whole cells used in the process were more stable and easier to prepare as compared with the isolated FDH from the cells. Kinetic study showed that the reaction rate was dependent on the concentration of cofactor, NAD(+), and that both R-HPBA and OPBA inhibited the reaction. A novel method for co-immobilization of whole cells and LDH enzyme on cotton cloth was developed using polyethyleneimine (PEI), which induced the formation of PEI-enzyme-cell aggregates and their adsorption onto cotton cloth, leading to multilayer co-immobilization of cells and enzyme with high loading (0.5 g cell and 8 mg LDH per gram of cotton cloth) and activity yield ( > 95%). A fibrous bed bioreactor with co-immobilized cells and enzyme on the cotton cloth was then evaluated for R-HPBA production in fed-batch and repeated batch modes, which gave relatively stable reactor productivity of 9 g/L . h and product yield of 0.95 mol/mol OPBA when the concentrations of OPBA and R-HPBA were less than 10 g/L.
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PMID:Biotransformation of R-2-hydroxy-4-phenylbutyric acid by D-lactate dehydrogenase and Candida boidinii cells containing formate dehydrogenase coimmobilized in a fibrous bed bioreactor. 1603 87

The survival of metazoan organisms is dependent upon the utilization of O2 as a substrate for COX (cytochrome c oxidase), which constitutes Complex IV of the mitochondrial respiratory chain. Premature transfer of electrons, either at Complex I or at Complex III, results in the increased generation of ROS (reactive oxygen species). Recent studies have identified two critical adaptations that may function to prevent excessive ROS production in hypoxic cells. First, expression of PDK1 [PDH (pyruvate dehydrogenase) kinase 1] is induced. PDK1 phosphorylates and inactivates PDH, the mitochondrial enzyme that converts pyruvate into acetyl-CoA. In combination with the hypoxia-induced expression of LDHA (lactate dehydrogenase A), which converts pyruvate into lactate, PDK1 reduces the delivery of acetyl-CoA to the tricarboxylic acid cycle, thus reducing the levels of NADH and FADH2 delivered to the electron-transport chain. Secondly, the subunit composition of COX is altered in hypoxic cells by increased expression of the COX4-2 subunit, which optimizes COX activity under hypoxic conditions, and increased degradation of the COX4-1 subunit, which optimizes COX activity under aerobic conditions. Hypoxia-inducible factor 1 controls the metabolic adaptation of mammalian cells to hypoxia by activating transcription of the genes encoding PDK1, LDHA, COX4-2 and LON, a mitochondrial protease that is required for the degradation of COX4-1. COX subunit switching occurs in yeast, but by a completely different regulatory mechanism, suggesting that selection for O2-dependent homoeostatic regulation of mitochondrial respiration is ancient and likely to be shared by all eukaryotic organisms.
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PMID:Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. 1755 2

In this work, a new kinetic method was proposed for quantification phenoxyl radicals generated in enzyme reaction. Instead of direct detecting the spectral signals of phenoxyl radicals, a molecular probe, the reduced form of nicotinamide adenine dinucleotide (NADH), was employed to indicate the formation of phenoxyl free radicals. It was found that the reactions of NADH and phenoxyl radicals are very fast, but can be followed by using stopped-flow fast scanning spectrophotometric technique. The initial rate of accelerated-oxidation of NADH represents the reactivity of phenoxyl free radical, which is proportional in a certain range to the initial concentration of the parent chlorophenols of the radicals. With this method, the phenoxyl radicals generated in oxidation reaction of chlorophenols (2-CP; 4-CP; 2,4-DCP; 2,4,6-TCP and 2,3,4,6-Tetra-CP) with hydrogen peroxide, catalyzed by horseradish peroxidase, were investigated. The method is highly sensitive. Phenoxyl radicals generated from as low as 1x10(-8)M 2,4-DCP, for example, can be readily detected with the proposed method. The results show that the reactivity of various phenoxyl radicals are in the following order: 2,4-DCP>4-CP>2-CP>2,4,6-TCP>2,3,4,6-Tetra-CP. A mechanism is proposed to explain the possible pathway of the probe reaction. The feasibility of this method was assessed by the determination of enzymatic generation of phenoxyl radicals in lake water samples.
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PMID:A new kinetic method for quantification phenoxyl free radicals. 1897 Jul 70

Assay of angiotensin I-converting enzyme (ACE) inhibitory activity always draws much attention because of diverse applications in the field of antihypertension and related pathogenesis. Recently, the use of a new synthetic substrate, 3-hydroxybutyrylglycyl-glycyl-glycine (3HB-GGG), for the assay of ACE inhibitory activity has been confirmed. To construct a rapid, economical, and automatic determination system of ACE inhibitory activity using 3HB-GGG, a flow injection analysis (FIA) system with enzymatic reactors was developed in this study. Enzyme reactors were composed of aminoacylase and 3-hydroxybutyrate dehydrogenase immobilized separately on CNBr-activated Sepharose 4B. The assay condition was optimized in terms of the conversion of 3HB-G into NADH by the enzymatic reactors when the reaction solution containing 3HB-G generated from 3HB-GGG (after the incubation with ACE) was repetitively injected into the FIA system. Under the optimized conditions, 3HB-G was converted to 3HB, and then 3HB was oxidized by NAD(+) to form NADH. The developed system successfully detected practical ACE inhibitors with a great sensitivity, high sampling frequency (10 samples h(-1)) and a durable stability of the enzymatic reactors.
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PMID:Flow injection analysis of angiotensin I-converting enzyme inhibitory activity with enzymatic reactors. 1961 21

Homofermentative production of reduced products requires additional reducing power output (NADH) from glucose catabolism. Anaerobic expression of the pyruvate dehydrogenase complex (PDH, encoded by aceEF-lpd, a normal aerobic operon) is able to provide the additional NADH required for production of reduced products in Escherichia coli fermentation. The multiple promoters (pflBp(1-7)) of pyruvate formate lyase (pflB) were evaluated for anaerobic expression of the aceEF-lpd operon. Four chromosomal constructs, pflBp(1-7)-aceEF-lpd, pflBp(1-6)-aceEF-lpd, pflBp(6,7)-aceEF-lpd, and pflBp6-aceEF-lpd efficiently expressed the PDH complex in anaerobically grown cells. Doubling the reducing power output was achieved when glucose was oxidized to acetyl-CoA through glycolysis and pyruvate oxidation by the anaerobically expressed PDH complex (glucose -->2 acetyl-CoA + 4 NADH). This additional reducing power output can be used for production of reduced products in anaerobic E. coli fermentation.
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PMID:Doubling the catabolic reducing power (NADH) output of Escherichia coli fermentation for production of reduced products. 1986 3

During anaerobic growth of Escherichia coli, pyruvate formate-lyase (PFL) and lactate dehydrogenase (LDH) channel pyruvate toward a mixture of fermentation products. We have introduced a third branch at the pyruvate node in a mutant of E. coli with a mutation in pyruvate dehydrogenase (PDH*) that renders the enzyme less sensitive to inhibition by NADH. The key starting enzymes of the three branches at the pyruvate node in such a mutant, PDH*, PFL, and LDH, have different metabolic potentials and kinetic properties. In such a mutant (strain QZ2), pyruvate flux through LDH was about 30%, with the remainder of the flux occurring through PFL, indicating that LDH is a preferred route of pyruvate conversion over PDH*. In a pfl mutant (strain YK167) with both PDH* and LDH activities, flux through PDH* was about 33% of the total, confirming the ability of LDH to outcompete the PDH pathway for pyruvate in vivo. Only in the absence of LDH (strain QZ3) was pyruvate carbon equally distributed between the PDH* and PFL pathways. A pfl mutant with LDH and PDH* activities, as well as a pfl ldh double mutant with PDH* activity, had a surprisingly low cell yield per mole of ATP (Y(ATP)) (about 7.0 g of cells per mol of ATP) compared to 10.9 g of cells per mol of ATP for the wild type. The lower Y(ATP) suggests the operation of a futile energy cycle in the absence of PFL in this strain. An understanding of the controls at the pyruvate node during anaerobic growth is expected to provide unique insights into rational metabolic engineering of E. coli and related bacteria for the production of various biobased products at high rates and yields.
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PMID:Metabolic flux control at the pyruvate node in an anaerobic Escherichia coli strain with an active pyruvate dehydrogenase. 2011 72


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